Project Summary/Abstract Proteomics research at the University of Kansas (KU) is limited by antiquated mass spectrometry instrumentation. This proposal requests $600,000 to acquire a new state-of-the-art Q Exactive HF mass spectrometer (1) coupled to an EASY-nLC 1200 chromatographic system for proteomics operations within the KU Mass Spectrometry Laboratory (MSL). The mass spectrometer combines a prefilter, a high performance quadrupole, and an ultra-high field Orbitrap analyzer. The primary rational for the requested instrument is that its analytical performance will enhance the research of NIH-funded scientists from six department at KU: Molecular Biosciences, Pharmacology and Toxicology, Medicinal chemistry, Chemistry, Pharmaceutical Chemistry and Ecology, and Evolutionally Biology. Additionally, as proteomics service of the KU MSL have expanded beyond the KU Campus, the requested instrument will impact the biological and health-related research of investigators at neighboring institutions such as Kansas State University (KSU), and the University of Kansas Medical Center (KUMC). Including these institutions brings the total number of regular users to 15. This proposal highlights several specific proteomics applications for each NIH-funded user that leverage the essential features of the requested instrument. The requested instrument will serves as an analytical workhorse for a wide variety of health-related research projects with the common focus of protein quantitative analysis in complex mixtures. Examples include, 1) quantitative protein up and down regulation in cancer cells deficient of Hsp90 using SILAC technology with the focus for low abundant kinases, 2) identification of SUMOylation substrates in primary hepatocytes under stress conditions that typically cause inflammation; 3) identification of partners in protein-protein interaction machinery relevant to mitochondrial neurodegeneration in Alzheimer's disease using mouse models.